PROJECT SUMMARY/ABSTRACT Pneumonia is currently diagnosed in over half a million U.S. emergency department (ED) visits by older adults each year with an ICU admission rate of 16% and 30-day mortality as high as 16%. However, we and others have found that the accurate diagnosis of pneumonia in ED older adults is inaccurate; emergency physician diagnostic uncertainty is present in 31% of patients, disagreement with inpatient physician occurs in ?47% of patients, and emergency physicians report they are uncomfortable diagnosing pneumonia in this population and they do not follow published guidelines. Under-diagnosis then leads to failure to treat and over- diagnosis exposes patients to treatment side effects and potential failure to treat the correct diagnosis. Emergency physician diagnostic uncertainty leads to increased admission rates, hospital length of stay, re- admission rates, and death within one year. We have found that dyspneic older adults are disproportionately affected by these challenges as 47% have pneumonia, CHF or COPD (the three most common causes of dyspnea) vs. 20% of younger patients. Therefore, improving emergency department pneumonia diagnosis accuracy specifically in older adults should be a priority. Biomarker testing has improved diagnostic accuracy in some causes of dyspnea in older adults (e.g. brain natriuretic peptide in acute CHF) and could improve pneumonia diagnosis. Antimicrobial peptides (AMPs) are key effectors of the innate immune system which increase with infection and can be excreted into the bloodstream in pneumonia. Our preliminary data suggests that two AMPs, Human ?-Defensin 5 (HD5) and Human ?-Defensin-2 (HBD2), are increased in dyspneic older ED adults with pneumonia. Further study is required to confirm these findings and determine their role in improving pneumonia diagnosis or to supplement current approaches as part of a clinical decision rule. This project seeks to (Aim #1) examine the existing risk stratification tools developed for other settings (Loeb Criteria, McGeer criteria, Centers for Disease Control, etc.) for their applicability to the ED setting alone and in combination with (Aim #2) antimicrobial peptides to improve diagnostic accuracy. If successful, this proposal will either identify an existing diagnostic tool that can be used in the ED or inform a future study to develop an ED-specific diagnostic tool.